DSP codes for the desmoplakin protein of the desmosome in the intercellular junction which is involved in force transmission in the myocardium and is also in the network of epithelial cells. DSP was first reported to be associated with palmoplantar epidermis, woolly hair, and dilated left ventricular cardiomyopathy (OMIM #605676). Rampazzo then described variants in Italian families with arrhythmogenic right ventricular dysplasia (ARVD) (PMID: 12373648). It is now known as the second most common genetic etiology of arrhythmogenic right ventricular cardiomyopathy (ARVC) PMID: 30915475. There have been occasional reports of DSP variants found in patients with HCM, however there is no conclusive evidence of pathogenicity of these variants in causing HCM, and there is no assertions of a disease mechanism despite rare variants being identified (PMID: 34500006). This gene-disease relationship was originally curated by the ClinGen Hypertrophic Cardiomyopathy GCEP in March 2017, and was given a classification of ‘no known disease relationship’ due to the absence of a clear assertion of disease causality in the literature. Upon recuration, by the Hereditary Cardiovascular Disease GCEP, they conferred a continued lack of supportive evidence for DSP in hypertrophic cardiomyopathy, and therefore updated the classification to DISPUTED. More evidence is needed to either support or entirely refute the role DSP plays in this HCM. This classification was approved by the ClinGen Hereditary Cardiovascular Diseases GCEP on April 13, 2022.
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